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Unveiling the enzymatic pathway of UMG-SP2 urethanase: insights into polyurethane degradation at the atomic level.

Chem Sci

December 2024

LAQV@REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto Rua do Campo Alegre s/n 4169-007 Porto Portugal

The recently discovered metagenomic urethanases UMG-SP1, UMG-SP2, and UMG-SP3 have emerged as promising tools to establish a bio-based recycling approach for polyurethane (PU) waste. These enzymes are capable of hydrolyzing urethane bonds in low molecular weight dicarbamates as well as in thermoplastic PU and the amide bond in polyamide employing a Ser-Ser -Lys triad for catalysis, similar to members of the amidase signature protein superfamily. Understanding the catalytic mechanism of these urethanases is crucial for enhancing their enzymatic activity and improving PU bio-recycling processes.

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A Rh(III)-catalyzed sequential C-H bond addition to dienes and in situ formed aldimines was developed, allowing for the preparation of otherwise challenging to access amines with quaternary centers at the -position. A broad range of dienes were effective inputs and installed a variety of aryl and alkyl substituents at the quaternary carbon site. Aryl and alkyl sulfonamide and carbamate nitrogen substituents were incorporated by using different formaldimine precursors.

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Targeted anticancer pre-vinylsulfone covalent inhibitors of carbonic anhydrase IX.

Elife

December 2024

Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.

We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: (1) primary sulfonamide group recognizing carbonic anhydrases (CA), (2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and (3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification.

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The standard protocol for Alloc group removal during peptide synthesis still presents limitations, including low reaction yields, -allylated byproducts, and the use of air-sensitive Pd(PPh). We addressed these challenges by developing a novel protocol using the air-stable Pd(PPh)Cl catalyst, Meldrum's acid (MA), and triethylsilane (TES-H). This combination ensured high yields, eliminated -allylated byproducts, and is compatible with automated synthesis.

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Public Health Risks Associated with Food Process Contaminants - A Review.

J Food Prot

December 2024

Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen 518060, China.

The increasing complexity of food production and processing has raised concerns regarding food process contaminants, which pose significant public health risks. Food process contaminants can be introduced during diverse phases of food processing such as drying, heating, grilling, and fermentation, resulting in the synthesis of harmful chemicals including acrylamide (AA), advanced glycation end products (AGEs), heterocyclic aromatic amines (HAAs), furan and its naturally occurring derivatives, polycyclic aromatic hydrocarbons (PAHs), N-nitroso compounds (NOCs), 2-chloropropane-1,2-diol esters (2-MCPDE), and 3-chloropropane-1,2-diol esters (3-MCPDE), ethyl carbamate (EC), glycidyl esters (GE), and 4-methylimidazole (4-MEI), all of these are harmful to human health. Although these compounds can be somewhat prevented during processing, eliminating them can often be challenging due to their unknown formation mechanism.

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